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It is known that blood pressure variability (BPV) can independently affect target organ damage (TOD), even with normal blood pressure. There have been few studieson chronic kidney disease (CKD) patients. We evaluated the relationship between BPV and TOD in a cross-sectional, multicenter study on hypertensive CKD patients. We evaluated 1,173 patients using 24-hr ambulatory blood pressure monitoring. BPV was defined as the average real variability, with a mean value of the absolute differences between consecutive readings of systolic blood pressure. TOD was defined as left ventricular hypertrophy (LVH) (by the Romhilt-Estes score ≥4 in electrocardiography) and kidney injury (as determined from an estimated glomerular filtration rate [eGFR]<30 mL/min/1.73 m(2) and proteinuria).The mean BPV of the subjects was 15.9±4.63 mmHg. BPV displayed a positive relationship with LVH in a univariate analysis and after adjustment for multi-variables (odds ratio per 1 mmHg increase in BPV: 1.053, P=0.006). In contrast, BPV had no relationship with kidney injury. These data suggest that BPV may be positively associated with LVH in hypertensive CKD patients.

Introduction: Patients with end-stage renal disease (ESRD) who are treated with hemodialysis (HD) frequently complain about hoarseness after completion of each HD session. The HD treatment affects laryngeal volume and muscle function. This study attempted to evaluate the vocal effect of HD by acoustic and aerodynamic analysis and to determine the difference between voice change group (VCG) and nonvoice change group (NVCG)., Materials and Methods: A total of 55 patients (34 females and 21 males) diagnosed with ESRD and undergoing outpatient HD were enrolled. The subjects were divided into the VCG (n=13) and NVCG (n=42) by the change of the Korean Voice Handicap Index score. Patients underwent weighing and acoustic, aerodynamic analysis before and after the HD. Fundamental frequency (F0), jitter, shimmer, noise-to-harmonics ratio (NHR), pitch range, habitual pitch, voice energy, and maximal phonation time (MPT) were obtained. The pre- and post-HD data were compared using paired t test. The results were compared after dividing the total group into the VCG and NVCG categories. Correlation between the change of the weight and change of the voice analysis result was certified by Pearson correlation coefficient., Results: The F0 and habitual pitch increased in all subjects. The NHR and MPT parameters significantly decreased (P<0.05). In the NVCG group, all the results were same as the total group. In the VCG group, the NHR result differed from the total group. All acoustic parameters showed no statistically significant differences between the two groups. There was no correlation between the weight change (%) and the change of acoustic parameter results., Conclusions: The NVCG group of patient displayed improvement in NHR, whereas the VCG group showed no change. Weight change did not significantly correlate with the voice analysis results., (Copyright © 2014 The Voice Foundation. Published by Mosby, Inc. All rights reserved.)

Aim: To investigate whether nonalcoholic fatty liver disease (NAFLD) affects coronary artery disease (CAD) and identify candidate mediators., Methods: Patients who underwent coronary angiography were consecutively recruited. The patients were classified into four groups by coronary artery stenosis: A, insignificant; B, one-vessel disease; C, two-vessel disease; and D, three-vessel disease. Abdominal ultrasonography was performed to determine the presence of a fatty liver and categorize by grade: 0, no evidence; 1, mild; 2, moderate; and 3, severe. We measured not only known CAD risk factors, but also serum insulin, HOMA-index, adiponectin, interleukin-6, tumor necrosis factor-α and high-sensitivity C-reactive protein levels., Results: Of the 134 patients who met the inclusion criteria, 82 (61.2%) had ultrasonographically diagnosed NAFLD. Among the 46 patients with CAD, 37 (80.4%) had evidence of a fatty liver. The two groups (A vs B-D) were significantly different in terms of age, total cholesterol, triglycerides, low-density lipoprotein levels and fatty liver. Coronary artery stenosis was strongly associated with fatty liver in a grade-dependent manner (P = 0.025). In binary logistic regression, NAFLD was a significant independent predictor of CAD (P = 0.03, OR = 1.685; 95%CI: 1.051-2.702). Among the candidate mediators, the serum adiponectin level showed a trend toward lowering based on CAD progression (P = 0.071)., Conclusion: NAFLD is an independent risk factor for CAD in a grade-dependent manner. Moreover, adiponectin might be related to the pathogenesis of NAFLD.

The kallikrein-kinin system (KKS) serves as the physiologic counterbalance to the renin-angiotensin system. This study was conducted to examine the changes in the expression of KKS components in podocytes under diabetic conditions and to elucidate the functional role of bradykinin (BK) in diabetes-associated podocyte apoptosis. Thirty-two rats were injected with either diluent (n = 16, C) or with streptozotocin intraperitoneally (n = 16, DM), and 8 rats from each group were treated with BK infusion for 6 weeks. Immortalized mouse podocytes were cultured in media containing 5.6 mmol/l glucose (NG), NG + 10(-7) mol/l AII (AII), or 30 mmol/l glucose (HG) with or without 10(-8) mol/l BK. Urinary albumin excretion was significantly higher in DM rats, and this increase was ameliorated by BK. Not only kininogen, kallikrein, and BK B1- and B2-receptor expression but also BK levels were significantly decreased in DM glomeruli and in cultured podocytes exposed to HG. The changes in the expressions of apoptosis-related molecules and the increase in the number of apoptotic cells in DM glomeruli as well as in HG- and AII-stimulated podocytes were significantly abrogated by BK. The suppressed KSS within podocytes under diabetic condition was associated with podocyte apoptosis, suggesting that BK may be beneficial in preventing podocyte loss in diabetic nephropathy.

End-stage renal disease patients have a higher risk for developing cancer. Although several causes for this increased risk have been proposed, the risk factors for cancer development in this population have not been elucidated. The aim of this study was to determine whether metabolic derangements, including insulin resistance and altered adipokines, increase the risk of developing malignancies in peritoneal dialysis (PD) patients, who are vulnerable to metabolic disorders because of excessive glucose absorbed from the dialysate. Study subjects comprised 106 nondiabetic PD patients who had been on PD for a minimum of 3 months with no overt malignancy. Baseline anthropometry, fasting glucose, insulin, and adiponectin were measured. The development of malignancy was evaluated during the follow-up period. During the mean follow-up of 47.0 ± 23.7 months, malignancy occurred in 15 patients (14.2%). The most common site of cancer was the kidney (26.7%), followed by thyroid (13.3%) and stomach (13.3%). Baseline insulin levels and homeostasis model assessment of insulin resistance were significantly higher, whereas plasma adiponectin levels were significantly lower, in patients who developed malignancy. Cox proportional hazards analysis revealed that insulin levels, homeostasis model assessment of insulin resistance, and lower adiponectin were independent predictors of malignancy. These findings demonstrate that insulin resistance and lower adiponectin levels could be risk factors for malignancy in nondiabetic PD patients., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Although various glomerular diseases in hantavirus infection have been reported, an association between hantavirus infection and crescentic glomerulonephritis has not been described. Herein, we report a case of immune complex-mediated crescentic glomerulonephritis in a 70-year-old man with Hantaan virus infection.

Background: The prevalence of chronic kidney disease (CKD) has been increasing throughout the world over the last decade. Metabolic syndrome (MS) has been known to be an independent risk factor of CKD. However, both renal and metabolic diseases are experienced differently in men and women, and clinical implication of MS on CKD may be different according to gender., Methods: To understand the association between MS and CKD, we performed a cross-sectional study in non-institutionalized civilians using the data of the Korean National Health and Nutrition Examination Survey. Of 37 769 participants, 5091 were available for the analysis of the prevalence of CKD (defined as dipstick proteinuria or a reduced GFR < 60 ml/min/1.73 m(2))., Results: The prevalence of CKD was 8.9% (7.4% in men, 4.7% in premenopausal women and 20.1% in postmenopausal women) and MS was seen in 26.2% (24.9% in men, 13.9% in premenopausal women and 52% in postmenopausal women). The prevalence of CKD increased with ageing, in particular after sharply after the age of 50 in both genders. MS was a significant determinant of CKD; however, sub-analysis revealed that MS was a risk factor for CKD only in men under the age of 60 and in postmenopausal women. Neither MS per se nor individual components of MS were associated with CKD in men over the age of 60 and in premenopausal women., Conclusion: Differential effect of MS on CKD according to age and gender in our study may provide a clue to define the subject in need for more attention for the treatment of MS in terms of the development of CKD.

Previous studies have shown that mineralocorticoid receptor (MCR) blocker reduces proteinuria in diabetic nephropathy (DN), but the role of aldosterone in podocyte injury has never been explored in DN. This study was undertaken to elucidate whether a local aldosterone system existed in podocytes and to examine its role in podocyte apoptosis under diabetic conditions. In vitro, immortalized podocytes were exposed to 5.6 mM glucose (NG), NG + 24.4 mM mannitol, and 30 mM glucose (HG) with or without 10(-7) M spironolactone (SPR). In vivo, 32 Sprague-Dawley rats were injected with diluent (C, n = 16) or streptozotocin intraperitoneally [diabetes mellitus (DM), n = 16], and 8 rats from each group were treated with SPR for 3 mo. Aldosterone synthase (CYP11B2) and MCR mRNA and protein expression were determined by real-time PCR and Western blot, respectively, and aldosterone levels by radioimmunoassay. Western blot for apoptosis-related molecules, Hoechst 33342 staining, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay were performed to determine apoptosis. CYP11B2 and MCR expression were significantly higher in HG-stimulated podocytes and DM glomeruli compared with NG cells and C glomeruli, respectively, along with increased aldosterone levels. Western blot analysis revealed that cleaved caspase-3 and Bax expression was significantly increased, whereas Bcl-2 expression was significantly decreased in HG-stimulated podocytes and in DM glomeruli. Apoptosis determined by Hoechst 33342 staining and TUNEL assay were also significantly increased in podocytes under diabetic conditions. These changes in the expression of apoptosis-related proteins and the increase in apoptotic cells were inhibited by SPR treatment. These findings suggest that a local aldosterone system is activated and is involved in podocyte apoptosis under diabetic conditions.

Recent studies have demonstrated that an inflammatory mechanism contributes to the pathogenesis of diabetic nephropathy (DN). It is also known that colchicine (Col) can prevent various renal injuries via its anti-inflammatory action. However, the effect of colchicine on DN has never been explored. This study was undertaken to elucidate the effect of colchicine on inflammation and extracellular matrix accumulation in DN. In vivo, 64 rats were injected with diluent (C; n = 32) or streptozotocin intraperitoneally (DM, n = 32). Sixteen rats from each group were treated with Col. In vitro, rat mesangial cells and NRK-52E cells were cultured in media with 5.6 mM glucose (NG) or 30 mM glucose (HG) with or without 10(-8) M Col. Monocyte chemotactic protein-1 (MCP-1) mRNA expression was determined by real-time PCR (RT-PCR), and the levels of MCP-1 in renal tissue and culture media were measured by ELISA. RT-PCR and Western blotting were also performed for intercellular adhesion molecule-1 (ICAM-1) and fibronectin (FN) mRNA and protein expression, respectively, and immunohistochemical staining (IHC) for ICAM-1, FN, and ED-1 with renal tissue. Twenty-four-hour urinary albumin excretion at 6 wk and 3 mo were significantly higher in DM compared with C rats (P < 0.05), and colchicine treatment significantly reduced albuminuria in DM rats (P < 0.05). Col significantly inhibited the increase in MCP-1 mRNA expression and protein levels under diabetic conditions both in vivo and in vitro. ICAM-1 and FN expression showed a similar pattern to the expression of MCP-1. IHC revealed that the number of ED-1(+) cells were significantly higher in DM compared with C kidney (P < 0.005), and this increase was significantly attenuated by Col treatment (P < 0.01). In conclusion, Col prevents not only inflammatory cell infiltration via inhibition of enhanced MCP-1 and ICAM-1 expression but also ECM accumulation in DN. These findings provide a new perspective on the renoprotective effects of Col in DN.

Monocyte chemoattractant protein-1 (MCP-1) is a potent chemokine that plays an important role in the recruitment of macrophages. Although previous studies have demonstrated the importance of MCP-1 in the pathogenesis of diabetic nephropathy (DN) in terms of inflammation, the role of MCP-1 and its receptor (C-C chemokine receptor 2; CCR2) in extracellular matrix (ECM) accumulation under diabetic conditions has been largely unexplored. This study was undertaken to investigate the functional role of the MCP-1/CCR2 system in high glucose-induced ECM (fibronectin and type IV collagen) protein expression in cultured mesangial cells (MCs). Mouse MCs were exposed to medium containing 5.6 mM glucose (NG), NG+24.4 mM mannitol (NG+M), or 30 mM glucose (HG) with or without mutant MCP-1 (mMCP-1), CCR2 small interfering (si)RNA, or CCR2 inhibitor (RS102895). To examine the relationship between MCP-1 and transforming growth factor (TGF)-beta1, MCs were also treated with TGF-beta1 (2 ng/ml) with or without mMCP-1 or CCR2 siRNA. Transient transfection was performed with Lipofectamine 2000 for 24 h. Cell viability was determined by an MTT assay, mouse and human MCP-1 and TGF-beta1 levels by ELISA, and CCR2 and ECM protein expression by Western blotting. Transfections of mMCP-1 and CCR2 siRNA increased human MCP-1 levels and inhibited CCR2 expression, respectively. HG-induced ECM protein expression and TGF-beta1 levels were significantly attenuated by mMCP-1, CCR2 siRNA, and RS102895 (P < 0.05). MCP-1 directly increased ECM protein expression, and this increase was inhibited by an anti-TGF-beta1 antibody. In addition, TGF-beta1-induced ECM protein expression was significantly abrogated by the inhibition of the MCP-1/CCR2 system (P < 0.05). These results suggest that an interaction between the MCP-1/CCR2 system and TGF-beta1 may contribute to ECM accumulation in DN.

Background: Peritoneal fibrosis (PF), a serious problem in long-term continuous ambulatory peritoneal dialysis (CAPD) patients, is characterized by extracellular matrix (ECM) accumulation which results from an imbalance between the synthesis and the degradation of ECM components. Previous studies have demonstrated that ECM synthesis is increased in human peritoneal mesothelial cells (HPMCs) under high glucose conditions, but the effects of high glucose on degradative pathways have not been fully explored. This study was undertaken to elucidate the effects of high glucose on these proteolytic processes in cultured HMPCs., Methods: HPMCs were isolated from human omentum and were exposed to 5.6 mM glucose (NG), 5.6 mM glucose +34.4 mM mannitol (NG + M), or 40 mM glucose (HG) with or without PKC inhibitor (PKCi). Real-time PCR and western blot were performed to determine collagenases (MMP-1, -8 and -13) and TIMPs (TIMP-1 and -2) mRNA and protein expression, respectively. The individual activities of collagenases in culture media were determined by ELISA., Results: Types I and III collagen protein expression were significantly increased in HG-conditioned media compared to NG media (P < 0.05). The MMP-1, -8 and -13/GAPDH mRNA ratios were significantly lower in HPMCs exposed to HG medium compared to NG cells by 64, 52 and 37%, respectively, and their protein expression by 76, 42 and 49%, respectively, in HG- vs NG-conditioned media. The activities of collagenases in HG-conditioned media were also significantly lower than those in NG media (P < 0.05). In contrast, HG significantly increased TIMPs mRNA ratios and protein expression in HPMCs. These changes in collagenase and TIMP expression induced by HG were abrogated upon pre-treatment with PKCi., Conclusion: In conclusion, impaired matrix degradation may contribute to ECM accumulation in PF.

Hepatocellular carcinoma (HCC) is one of the most common malignancies. Many factors are considered to be etiology associated with HCC; the important factors are hepatitis B and C viruses and alcohol. Cirrhosis is present in the majority of patients with HCC. It is assumed that all diseases, which lead to liver cirrhosis, may be complicated by the development of HCC. We report a 36-year-old man with HCC which developed from cardiac cirrhosis caused by constrictive pericarditis in whom both hepatitis B virus and hepatitis C viral marker tests were all negative. CT scan of his heart showed pericardial calcification with diastolic dysfunction of right ventricle. Abdominal CT scan revealed mottled mosaic pattern of contrast enhancement of liver parenchyme and two hepatic lesions that were considered to be HCCs. Left lateral segmentectomy of liver was performed. There were two well-circumscribed masses which were confirmed to be HCC and the remaining hepatic parenchyma showed bridging fibrosis between central zonal regions. To our knowledge, this is the first case of HCC complicating cardiac cirrhosis in Korea.

Background: Proteinuria is a cardinal feature of glomerular disease, including diabetic nephropathy, and the glomerular filtration barrier acts as a filter, restricting protein excretion in urine. We tested whether the expression of P-cadherin, a molecule known to be located at the slit diaphragm, was altered by diabetes in vivo and by high glucose in vitro., Methods: In vivo, 24 Sprague-Dawley rats were injected with diluent [control (C), n=8] or streptozotocin intraperitoneally and the latter were left untreated (DM, n=8) or treated with insulin (DM+I, n=8) for 6 weeks. In vitro, immortalized mouse podocytes were cultured in media with 5.6 mM glucose (LG), LG+19.4 mM mannitol (LG+M) or 25 mM glucose (HG) with or without protein kinase C (PKC) inhibitor (10(-7) M calphostin C or 10(-6) M GF 109203X). Reverse transcription-polymerase chain reaction, western blotting for P-cadherin mRNA and protein expression, respectively, were performed with sieved glomeruli and cell lysates, and immunofluorescence staining was undertaken with renal tissue., Results: Twenty-four hour urinary albumin excretion was significantly higher in DM compared with C and DM+I rats (P<0.05). Glomerular P-cadherin mRNA expression was significantly lower in DM (1.36+/-0.20x10(-2) attm/ng RNA) than in C rats (2.61+/-0.33x10(-2) attm/ng RNA) (P<0.05). P-Cadherin protein expression, assessed by western blot and immunofluorescence staining, was also decreased in DM compared with C and DM+I glomeruli. HG significantly reduced P-cadherin mRNA and protein expression in cultured podocytes by 42% and 62%, respectively (P<0.05), and these decrements were ameliorated by PKC inhibitor., Conclusions: Diabetes in vivo and exposure of podocytes to HG in vitro reduced P-cadherin mRNA and protein expression, and PKC was involved in the regulation of HG-induced down-regulation of P-cadherin. These findings suggest that the decrease in P-cadherin expression is connected with the early changes of diabetic nephropathy and, thus, may contribute to the development of proteinuria.

Background: Diabetic nephropathy is characterized by glomerular and tubular hypertrophy, and angiotensin II receptor blockers (ARBs) are known to prevent renal hypertrophy in diabetic patients., Methods: To determine the effect of ARB on podocyte p27(Kip1) mRNA and protein expression, podocytes were exposed to 5.6 mmol/L normal glucose or 25 mmol/L high glucose with or without ARB, 10(-7) mol/L L-158,809. For animal studies, streptozotocin-induced diabetic rats were left untreated or were treated with 1 mg/kg/day L-158,809 for 3 months (diabetes mellitus + ARB). Competitive reverse transcription-polymerase chain reaction (RT-PCR), Western blot, immunohistochemistry, and morphometric analyses were performed., Results: p27(Kip1) mRNA and protein expression in podocytes exposed to high glucose and in 3-month diabetic glomeruli were significantly increased (P < 0.01). High glucose significantly increased angiotensin II levels both in cell lysates and in media compared with normal glucose (P < 0.05) and exogenous angiotensin II also increased p27(Kip1) mRNA and protein expression in podocytes. L-158,809 treatment in podocytes inhibited the increase in p27(Kip1) mRNA expression by 84%, and protein expression by 89% (P < 0.05). p27(Kip1) mRNA and protein expression in diabetic + ARB glomeruli were also significantly reduced by 78% and 85%, respectively, compared with diabetic glomeruli (P < 0.01). ARB treatment also significantly ameliorated increased glomerular p27(Kip1) expression in diabetes mellitus as assessed by immunohistochemistry (P < 0.01). The increase in glomerular volume in diabetes mellitus was also inhibited by 81% with ARB treatment (P < 0.05)., Conclusion: p27(Kip1) mRNA and protein expression were increased in diabetic glomeruli as well as in high glucose-stimulated podocytes, and this increment in p27(Kip1) expression was ameliorated by ARB treatment. These findings indicate that ARB treatment has an additional effect on preventing renal hypertrophy in diabetes mellitus.

Background: In recent years, the rate of peritonitis during continuous ambulatory peritoneal dialysis (CAPD) has been significantly reduced. However, peritonitis remains a major complication of CAPD, accounting for considerable mortality and hospitalization among CAPD patients., Objective: To generate a "center tailored" treatment protocol for CAPD peritonitis by examining the changes of causative organisms and their susceptibilities to antimicrobial agents over the past 10 years., Method: Retrospective review of the medical records of 1015 CAPD patients (1108 episodes of peritonitis) who were followed up from 1992 through 2001., Results: The overall incidence of peritonitis was 0.40 episodes/patient-year. The annual rate of peritonitis and the incidence of peritonitis caused by a single gram-positive organism were significantly higher in 1992 and 1993 compared with those in the rest of the years (p < 0.05). The incidence of peritonitis due to coagulase-negative staphylococcus (CoNS) decreased significantly over time, whereas there was no significant change in the incidence of Staphylococcus aureus (SA)-induced peritonitis. Among CoNS, resistance to methicillin increased from 18.4% in 1992-1993 to 41.7% in 2000-2001 (p < 0.05). In contrast, the incidence of methicillin-resistant SA was not different according to the calendar year. Catheter removal rates were significantly higher in peritonitis due to a single gram-negative organism (16.6%) compared with gram-positive peritonitis (4.8%, p < 0.005). The mortality associated with peritonitis was also higher in gram-negative (3.7%) compared with gram-positive peritonitis (1.4%), but there was no statistical significance. Among single gram-positive organism-induced peritonitis, catheter removal rates were significantly higher in SA (9.3%) than those in CoNS (2.9%, p < 0.01) and other gram-positive organisms (2.9%, p < 0.05). In peritonitis caused by CoNS, the methicillin-resistant group showed significantly higher removal rates than the methicillin-susceptible group (8.2% vs 1.0%, p < 0.01)., Conclusion: The incidence of peritonitis for 2001 decreased to less than half that for 1992, due mainly to a significant decrease in CoNS-induced peritonitis, whereas the proportions of peritonitis due to a single gram-negative organism and methicillin-resistant CoNS increased. These findings suggest that it is necessary to prepare new center-based guidelines for the initial empirical treatment of CAPD peritonitis.